Modulation of Endothelial Cell Morphogenesis in Vitro by MMP-9 During Glial-Endothelial Cell Interactions

Clin Exp Metastasis. 2000;18(4):337-42. doi: 10.1023/a:1010833730407.


The purpose of this study was to investigate the roles of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the formation of capillary structures by human brain microvascular endothelial cells cocultured with SNB19 glioblastoma cells. Unstimulated cocultures did not form capillaries and produce MMP-9 but stimulation with the protein kinase C (PKC) activator 4-phorbol-12-myristate 13-acetate (PMA) produced MMP-9 and capillary networks. Addition of recombinant MMP-9 increased capillary formation. Anti-MMP-9 antibodies, TIMP-1, the synthetic MMPs inhibitor Batimastat (BB-94), and the PKC inhibitor calphostin-C all reduced MMP-9 activity and capillary network formation in these cocultures. Cytochalasin-D in the presence of PMA suppressed MMP-9 expression and capillary formation, but colchicine-B had no such effect. Finally, PMA-induced MMP-9 expression and capillary formation were inhibited by the MEKK-specific inhibitor PD98059. These results suggest that MMP-9 is important in endothelial cell morphogenesis and the formation of capillaries in glial/endothelial cocultures in vitro.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Brain / blood supply*
  • Capillaries
  • Carcinogens / pharmacology
  • Cell Communication / physiology*
  • Cells, Cultured
  • Endothelium, Vascular / cytology*
  • Humans
  • Matrix Metalloproteinase 9 / physiology*
  • Microcirculation
  • Neovascularization, Physiologic
  • Neuroglia / physiology*
  • Protein Kinase C / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tissue Inhibitor of Metalloproteinase-1 / physiology*


  • Carcinogens
  • Tissue Inhibitor of Metalloproteinase-1
  • Protein Kinase C
  • Matrix Metalloproteinase 9
  • Tetradecanoylphorbol Acetate